Rationale and design of the EXenatide Study of Cardiovascular Event Lowering (EXSCEL) trial

Rury R. Holman, Mary Angelyn Bethel, Jyothis George, Harald Sourij, Zoë Doran, Joanne Keenan, Nardev S. Khurmi, Robert J. Mentz, Abderrahim Oulhaj, John B. Buse, Juliana C. Chan, Nayyar Iqbal, Sudeep Kundu, Aldo P. Maggioni, Steven P. Marso, Peter Öhman, Michael J. Pencina, Neil Poulter, Lisa E. Porter, Ambady RamachandranBernard Zinman, Adrian F. Hernandez

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Exenatide once-weekly is an extended release formulation of exenatide, a glucagon-like peptide–1 receptor agonist, which can improve glycemic control, body weight, blood pressure, and lipid levels in patients with type 2 diabetes mellitus (T2DM). The EXenatide Study of Cardiovascular Event Lowering (EXSCEL) will compare the impact of adding exenatide once-weekly to usual care with usual care alone on major cardiovascular outcomes. EXSCEL is an academically led, phase III/IV, double-blind, pragmatic placebo-controlled, global trial conducted in 35 countries aiming to enrol 14,000 patients with T2DM and a broad range of cardiovascular risk over approximately 5 years. Participants will be randomized (1:1) to receive exenatide once-weekly 2 mg or matching placebo by subcutaneous injections. The trial will continue until 1,360 confirmed primary composite cardiovascular end points, defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, have occurred. The primary efficacy hypothesis is that exenatide once-weekly is superior to usual care with respect to the primary composite cardiovascular end point. EXSCEL is powered to detect a 15% relative risk reduction in the exenatide once-weekly group, with 85% power and a 2-sided 5% alpha. The primary safety hypothesis is that exenatide once-weekly is noninferior to usual care with respect to the primary cardiovascular composite end point. Noninferiority will be concluded if the upper limit of the CI is <1.30. EXSCEL will assess whether exenatide once-weekly can reduce cardiovascular events in patients with T2DM with a broad range of cardiovascular risk. It will also provide long-term safety information on exenatide once-weekly in people with T2DM. ClinicalTrials.gov Identifier: NCT01144338

Original languageEnglish (US)
Pages (from-to)103-110
Number of pages8
JournalAmerican Heart Journal
Volume174
DOIs
StatePublished - Apr 1 2016

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Type 2 Diabetes Mellitus
exenatide
Placebos
Safety
Subcutaneous Injections
Risk Reduction Behavior
Stroke
Myocardial Infarction
Body Weight
Blood Pressure
Lipids

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Holman, R. R., Bethel, M. A., George, J., Sourij, H., Doran, Z., Keenan, J., ... Hernandez, A. F. (2016). Rationale and design of the EXenatide Study of Cardiovascular Event Lowering (EXSCEL) trial. American Heart Journal, 174, 103-110. https://doi.org/10.1016/j.ahj.2015.12.009

Rationale and design of the EXenatide Study of Cardiovascular Event Lowering (EXSCEL) trial. / Holman, Rury R.; Bethel, Mary Angelyn; George, Jyothis; Sourij, Harald; Doran, Zoë; Keenan, Joanne; Khurmi, Nardev S.; Mentz, Robert J.; Oulhaj, Abderrahim; Buse, John B.; Chan, Juliana C.; Iqbal, Nayyar; Kundu, Sudeep; Maggioni, Aldo P.; Marso, Steven P.; Öhman, Peter; Pencina, Michael J.; Poulter, Neil; Porter, Lisa E.; Ramachandran, Ambady; Zinman, Bernard; Hernandez, Adrian F.

In: American Heart Journal, Vol. 174, 01.04.2016, p. 103-110.

Research output: Contribution to journalArticle

Holman, RR, Bethel, MA, George, J, Sourij, H, Doran, Z, Keenan, J, Khurmi, NS, Mentz, RJ, Oulhaj, A, Buse, JB, Chan, JC, Iqbal, N, Kundu, S, Maggioni, AP, Marso, SP, Öhman, P, Pencina, MJ, Poulter, N, Porter, LE, Ramachandran, A, Zinman, B & Hernandez, AF 2016, 'Rationale and design of the EXenatide Study of Cardiovascular Event Lowering (EXSCEL) trial', American Heart Journal, vol. 174, pp. 103-110. https://doi.org/10.1016/j.ahj.2015.12.009
Holman, Rury R. ; Bethel, Mary Angelyn ; George, Jyothis ; Sourij, Harald ; Doran, Zoë ; Keenan, Joanne ; Khurmi, Nardev S. ; Mentz, Robert J. ; Oulhaj, Abderrahim ; Buse, John B. ; Chan, Juliana C. ; Iqbal, Nayyar ; Kundu, Sudeep ; Maggioni, Aldo P. ; Marso, Steven P. ; Öhman, Peter ; Pencina, Michael J. ; Poulter, Neil ; Porter, Lisa E. ; Ramachandran, Ambady ; Zinman, Bernard ; Hernandez, Adrian F. / Rationale and design of the EXenatide Study of Cardiovascular Event Lowering (EXSCEL) trial. In: American Heart Journal. 2016 ; Vol. 174. pp. 103-110.
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